An unclassified variant of CHD7 activates a cryptic splice site in a patient with CHARGE syndrome

Abstract

CHARGE syndrome is a rare autosomal dominant disease that is typically caused by heterozygous CHD7 mutations. A de novo variant in a CHD7 splicing acceptor site (NM_017780.3:c.7165–4A>G) was identified in a Japanese boy with CHARGE syndrome. This variant has been considered to be an “unclassified variant” due to its position outside the consensus splicing sites. In this study, abnormal splicing derived from this known variant was confirmed by cDNA sequencing.

Recurrent de novo MAPK8IP3 variants cause neurological phenotypes

“…Exome sequencing was performed as previously reported in three institutions: Tohoku University, the National Center for Child Health and Development, and Yokohama City University.…”

De Novo Duplication in the CHD7 Gene Associated With Severe CHARGE Syndrome

“…Alterations in CHD7 have been identified in more than two-third of all children, who fulfil the clinical diagnostic criteria for CHARGE syndrome. 16–18 Truncating variants including nonsense, frameshift, and splice variants (89%) that typically result in haploinsufficiency are the most frequently encountered followed by missense (8%) variants. 17,19,20 CHD7 encodes a chromodomain helicase DNA-binding protein, which plays a significant role in early embryonic development and controls gene expression via chromatin remodelling during the cell cycle.…”

CHARGE syndrome associated with de novo (I1460Rfs*15) frameshift mutation of CHD7 gene in a patient with arteria lusoria and horseshoe kidney

“…It is important for each novel mutation that extends the spectrum of pathogenic mutations in the CHD7 gene to be included in the databases, to facilitate the diagnosis and estimate the prevalence of the disorder (3). Since the publication of the new criteria in 2016, only a few case reports discussing patients with CHARGE syndrome with a pathogenic mutation in the CHD7 gene, previously considered as atypical CHARGE, have been published (9,10). By understanding the different genotypes of CHARGE syndrome, it was possible to make clear genotype-phenotype associations for all CHD7 variants.…”